Recent observations have demonstrated that some forms of osteogenesis imperfecta and Ehlers-Danlos Syndrome are caused by genetically determined alterations in the structure of Type I procollagen. The present proposal is to use recombinant DNA technology in order to exploit and extend these observations. Specifically, the aims are (1) to determine the nucleotide sequence of the mutation in a patient with OI whose fibroblasts have recently been shown to synthesize a Type I procollagen with a structure alteration in its C-propeptide; (2) to determine the nucleotide sequence of the mutation in a patient with EDS-VII whose fibroblasts synthesize a Type I procollagen with a structural alteration in the N-terminal region of its pro-alpha-2 chain; (3) to define the mutation in a patient with OI whose fibroblasts do not express the gene for pro-alpha-2 chains; (4) to determine the nucleotide sequences of mutations in other patients with OI or EDS whose fibroblasts are found to synthesize structurally abnormal Type I procollagen; and (5) to explore the feasibility of developing new recombinant DNA tests for OI and EDS.